Fermentation processes for preparing D-pantothenic acid by microorganisms have been disclosed in great number, including by EP 0 590 857, WO 96/33283; U.S. Pat. No. 6,013,492, WO 97/10340, DE 198 46 499, EP 1 001 027, EP 1 006 189, EP 1 006 192 and EP 1 006 193.
Thus EP 1 006 189 and EP 1 001 027 describe processes for preparing pantothenate in which the fermentation solution reaches a content of at most 1 g/l of D-pantothenic acid. However, such low pantothenic acid contents in the fermentation solution, that is to say less than 10% by weight based on the solids content, are unsuitable for economic production of D-pantothenic acid-containing animal feed supplements. A further disadvantage of the processes described to date is that isolating the product from the fermentation medium requires numerous complex work-up steps. An economic production process for the industrial scale has not been disclosed.
In the German laid-open application DE 100 16 321, a fermentation process is described for producing a D-pantothenic-acid-containing animal feed supplement. However, a significant disadvantage of this process, as also with the fermentation processes cited above for D-pantothenic acid production, is that the pantothenic acid precursor β-alanine has to be supplied to the microorganism via the fermentation medium in order to obtain economic yields of the desired product.
In addition U.S. Pat. No. 6,013,492 and WO 96/332839 describe the work-up of D-pantothenic acid from the fermentation solution by filtering off insoluble constituents (e.g. cell material) from the culture medium, adsorbing the filtrate to activated carbon, subsequently eluting the D-pantothenic acid with an organic solvent, preferably methanol, neutralizing the eluent with calcium hydroxide, and finally crystallizing calcium D-pantothenate. Significant disadvantages are the losses of product of value which occur during the crystallization and the use of an organic solvent which may be removed from the product only with difficulty and requires complex solvent recovery.
EP 0 590 857 describes a fermentation process for producing D-pantothenic acid in which culturing a microorganism obligatorily requires supply of β-alanine. The fermentation solution is filtered to separate off the biomass, then passed through a cationic exchanger and then through an anionic exchanger, is then neutralized with calcium hydroxide, concentrated by evaporation, admixed with activated carbon, filtered once more and crystallized with addition of methanol and calcium chloride. The resultant calcium-pantothenate-containing product, in addition to D-pantothenic acid in the form of the calcium salt, also contains calcium chloride in a molar ratio of 1:1. To reduce the calcium chloride content, electrodialysis with subsequent spray-drying is necessary. This process has the disadvantage, because of the multiplicity of complex process steps and the use of organic solvents, of being neither economic nor ecological.